Polyozellin, a New Inhibitor of Prolyl Endopeptidase from Polyozellus multiplex.

Hwang, Ji-Sook; Song, Kyung‐Sik; Kim, Won-Oon; Lee, Tae‐Ho; Koshino, Hiroyuki; Yoo, Ick Dong

doi:10.7164/antibiotics.50.773

Cited by 46 publications

(37 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relatively large quantities of polyozellin (0.0134-0.0553 %) present in the dried aerial parts of the P.multiplex have led to the production of extracts for use in food [23,24]. In this study, the effects of polyozellin (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Polyozellin was prepared as described previously [23,24]. Bacterial lipopolysaccharide (LPS, serotype: 0111:B4, L5293, used at 100 ng/mL), Evans blue, and crystal violet were obtained from Sigma (St. Louis, MO, USA).…”

Section: Reagentsmentioning

confidence: 99%

“…However, our previous study determined that polyozellin effectively induced Phase II enzymes, but not thelephoric acid which has catechol moieties as in the case of polyozellin [18]. In addition, the activity of prolyl endopeptidase was inhibited by polyozellin (IC 50 = 2.72 lM), but not thelephoric acid, in vitro study [23]. On the other hand, both polyozellin and thelephoric acid showed similar anti-oxidative activities against a,a-diphenyl-b-picrylhydrazyl (DPPH), H 2 O 2 , hydroxyl radical, and superoxide anion, at 10 and 100 lM [24].…”

Section: Protective Effect Of Polyozellin In the Clp-induced Pulmonarmentioning

confidence: 99%

See 2 more Smart Citations

Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses

Yang

Lee

et al. 2015

Inflamm. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Reagentsmentioning

confidence: 99%

Section: Protective Effect Of Polyozellin In the Clp-induced Pulmonarmentioning

confidence: 99%

See 1 more Smart Citation

Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses

Yang

Lee

et al. 2015

Inflamm. Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…2, 1 and 2 showed inhibitory activity on S. pneumoniae FabK in a dose-dependant fashion with IC 50 values of 0.24 and 1.57 m M, respectively, while their structurally-related compounds, polyozellin (3) we previously isolated [15] and commercially available 2,5-dihydroxy-1,4-benzoquinone (4), did not inhibit the FabK even at 100 m M. It suggests that both the 2,5-dihydroxy-1,4-benzoquinone and the phenol moieties could be important for their activity. To elucidate the mechanism of inhibition by 2 on the FabK, a lineweaver-burk plot analysis was conducted (Fig.…”

mentioning

confidence: 94%

Atromentin and Leucomelone, the First Inhibitors Specific to Enoyl-ACP Reductase (FabK) of Streptococcus pneumoniae

2006

View full text Add to dashboard Cite

Two potent inhibitors of FabK, the enoyl-acyl carrier protein (ACP) reductase of Streptococcus pneumoniae, were isolated from the solid state fermentation of an unidentified fungus F010248. Their structures were identified to be atromentin and leucomelone by various spectral analysis. Atromentin and leucomelone inhibited the FabK with IC 50 values of 0.24 and 1.57 mM, respectively, while did not inhibit FabI, the enoyl-ACP reductase of either Escherichia coli or Staphylococcus aureus, even at 200 mM. Atromentin and leucomelone are the first inhibitors specific to the enoyl-ACP reductase (FabK) of Streptococcus pneumoniae.Keywords atromentin, leucomelone, terphenyl, enoyl-ACP reductase, FabK, Streptococcus pneumoniae Fatty acid biosynthesis in bacteria is essential to the production of a number of lipid-containing components including the cell membrane. The bacterial fatty acid system (FAS II) utilizes discrete monofunctional enzymes that operate in conjunction with acyl carrier protein (ACP)-associated substrates. Mammalian fatty acid synthase (FAS I) differs from FAS II in that lipid biosynthesis is mediated by a single multifunctional enzyme-ACP complex. The differences in prokaryote and eukaryote fatty acid biosynthesis offer an attractive opportunity for selective FASII inhibition which is a potential strategy for the development of antibacterial agents [1ϳ3]. Bacterial enoyl-ACP reductase that catalyzes the final and rate-limiting step in the type II FAS has been validated as a novel target for antibacterial drug development. Indeed, the antibacterial target of triclosan [4], the broad spectrum biocide in a wide range of consumer goods, and isoniazid [5], used in the treatment of tuberculosis for 50 years, have been determined to be the FabI. There are three isoforms, FabI, FabK, and FabL, in enoyl-ACP reductase. FabI is widely distributed in most of bacteria but, FabK is present in few important pathogens such as Streptococcus pneumoniae, Enterococcus faecalis, Clostridium acetobutylicum and Pseudomonas aeruginosa. E. faecalis and P. aeruginosa were known to contain FabI as well as FabK. Therefore, FabK inhibitors will be promising as an antibacterial drug specific to the important respiratory pathogen S. pneumonia and required for enoyl reductase therapy to be effective on E. faecalis and P. aeruginosa [6ϳ8]. Although there have been a number of reports on the designing and development of FabI inhibitors [9ϳ11], little has been studied for FabK inhibitors. In the course of the screening program for FabK inhibitors from microbial resources, two terphenyl type compounds were isolated from the solid state fermentation of an identified fungus F010248. They are identified as atromentin (1) and leucomelone (2) by spectral analysis. We report here the isolation and FabK-specific inhibitory activity of 1 and 2 (Fig. 1).The fungal stain F010248 was isolated from a soil sample that was collected in a corn field around Kongjucity, Chungchongnam-do, Korea. Fermentation was carried out in a liquid culture med...

show abstract

“…Previous studies have demonstrated that polyozellin exhibits a variety of biological activities, including the inhibition of prolyl endopeptidase (Hwang et al, 1997), and antioxidant and anticancer properties (Kim et al, 2004). Several natural antioxidant compounds are known to reduce inflammation.…”

Section: Introductionmentioning

confidence: 99%

Polyozellin blocks tumor necrosis factor α-induced interleukin 8 and matrix metalloproteinase 7 production in the human intestinal epithelial cell line HT-29

et al. 2011

Self Cite

View full text Add to dashboard Cite

Polyozellin isolated from Polyozellus multiplex (Thelephoraceae) displays potent anti-inflammatory effects in murine macrophages. Here we evaluated whether polyozellin has the potential to ameliorate diseases characterized by mucosal inflammation in intestinal epithelial HT-29 cells. Polyozellin significantly inhibited tumor necrosis factor (TNF)-α-induced interleukin-8 secretion and mRNA expression. Moreover, polyozellin suppressed the expression of matrix metalloproteinase-7 mRNA and extracellular pro-matrix metalloproteinase-7 secretion. A signal transduction study revealed that polyozellin significantly attenuates TNF-α-mediated p38 phosphorylation, inhibitory factor κBα degradation, and nuclear factor-κB-mediated transcriptional activation. Collectively, these results suggest that polyozellin has the potential to attenuate intestinal inflammation and shed light on the novel signal pathway evoked by TNF-α during intestinal inflammation.

show abstract

Polyozellin, a New Inhibitor of Prolyl Endopeptidase from Polyozellus multiplex.

Cited by 46 publications

References 21 publications

Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses

Inhibitory effects of polyozellin from Polyozellus multiplex on HMGB1-mediated septic responses

Atromentin and Leucomelone, the First Inhibitors Specific to Enoyl-ACP Reductase (FabK) of Streptococcus pneumoniae

Polyozellin blocks tumor necrosis factor α-induced interleukin 8 and matrix metalloproteinase 7 production in the human intestinal epithelial cell line HT-29

Contact Info

Product

Resources

About